Journal of Clinical and Aesthetic Dermatology

Psoriasis and Cutaneous Supplement 2016

An evidence-based, peer-reviewed journal for practicing clinicians in the field of dermatology

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S 1 8 S U P P L E M E N T T O T H E J O U R N A L O F C L I N I C A L A N D A E S T H E T I C D E R M AT O L O G Y [ S E P T E M B E R 2 0 1 6 • V O L U M E 9 • N U M B E R 9 ] 17A as a potential target in the treatment of PsA. The FUTURE-2 study was a Phase 3, double-blind, placebo-controlled, multicenter study of 397 PsA patients randomized to be treated with subcutaneous placebo or secukinumab (300, 150, or 75mg) weekly from baseline to Week 4, then once every four weeks thereafter. 122 At 24 weeks, significantly more secukinumab patients achieved an ACR20 score versus placebo patients (54%, 51%, 29%, and 15% for secukinumab 300, 150, and 75mg for placebo, respectively). Serious adverse events were reported by 5, 1, and 4 percent of secukinumab patients (300, 150, 75mg, respectively) compared to two percent in the placebo group. In a Phase 3 clinical trial, 417 biologic disease- modifying antirheumatic drug (bDMARD)-naïve PsA patients were randomized to receive placebo; adalimumab 40mg once every two weeks (active control); or another anti-IL-17A monoclonal antibody, ixekizumab, at a dose of 80mg every two or every four weeks after an initial 160mg dose at Week 0. At 12 and 24 weeks, significantly more ixekizumab patients achieved ACR20, ACR50, ACR70 scores or PASI 75, PASI 90, and PASI 100 responses than placebo (p<0.01 all comparisons to placebo). 123 Ixekizumab patients in both groups also experienced significantly greater reductions in dactylitis at Weeks 12 and 24 than placebo patients, but not for enthesitis. Efficacy for adalimumab was also observed. Treatment-emergent adverse events occurred significantly more often (p<0.05) in both adalimumab and ixekizumab groups compared to placebo. Both active treatments resulted in inhibition of radiographic progression of structural joint damage compared to placebo (p<0.025). 124 Apremilast, an oral phosphodiesterase-4 inhibitor, has been approved for the treatment of PsA based on data including that from the PALACE-1 trial. A total of 504 patients with active PsA and prior DMARD and/or biologic therapy were randomized to be treated with placebo or apremilast 20mg twice daily or apremilast 30mg twice daily. 125 At 16 weeks, significantly more apremilast 20mg (31%) and 30mg (40%) patients achieved ACR20 compared to placebo (19%), p<0.001. Data were recently presented on two-year follow-up of these patients indicating durable ACR20 results to 104 weeks (65.3% and 60.9% for 30 and 20mg, twice daily, respectively). The clinical treatment of PsA patients requires a careful and individualized assessment of the patient. Clinicians must take a detailed patient history to know what other treatments the patient has taken, patient preferences, prognostic factors, disease involvement, comorbidities, and the patient's activity levels and lifestyle considerations. The Group for Research and Assessment of Psoriasis and Psoriatic Arthritis (GRAPPA) recently published treatment recommendations for PsA based on the following six key domains or principles: arthritis, spondylitis, enthesitis, dactylitis, skin disease, nail disease, and comorbidities. 126 The clinical importance of addressing comorbidities in PsA is increasingly recognized. The main comorbidities associated with PsA recently recognized by the Canadian Dermatology-Rheumatology Comorbidity Initiative include the risk of cardiovascular disease, smoking, obesity, malignancies (either new cancer or recurrence), infections, osteoporosis, and depression. 127 For brevity, their comorbidity list did not include some other conditions, such as asthma, chronic kidney disease, hypertension, or manifestations associated with systemic disease, for example, uveitis. The Canadian recommendations were comprehensive and multidisciplinary and represent a new, approach of this important topic. Limitations of these recommendations are that clinical trial evidence is sometimes weak and it is unclear how these recommendations should translate into changes in real-world clinical practice. Further study of PsA is warranted, and there are important considerations for those designing clinical trials in order to result in highly relevant data to guide modern clinical practice. Clinical trials must select the specific domain(s) to be assessed and, if multiple domains are addressed, how they combine. 128 Outcome metrics must be selected that are clinically relevant and understandable, as well as the optimal imaging techniques. Most studies evaluate patients with active PsA and there should be more effort to evaluate early PsA. Study outcomes may describe low disease activity or remission, but careful and objective definitions should be clarified. When patients reach their therapeutic goal, studies should help clinicians understand how to taper or discontinue therapy appropriate to maintain results. Finally, the role of biomarkers should be explored to better understand individual patient risks and needs. CUTANEOUS ONCOLOGY Paradigm Shifts in Cutaneous Oncology There are currently several topical treatments for field actinic keratosis (AK) approved by the FDA for use in the United States. These are 5-fluorouracil (available in 0.5%, 1%, and 5% formulations), imiquimod (2.5%, 2.75%, and 5% formulations), diclofenac, photodynamic therapy (PDT) with 5-aminolevulinic acid (ALA) or methyl aminolevulinate (MAL), and ingenol mebutate (0.015% and 0.05% formulations). Among the recent breakthroughs in dermatology, the paradigm shift in how field AK is treated is an important change. While most field AK is treated with cryotherapy and sometimes adjunctive topical treatments, topical treatments are infrequently used as monotherapy. This is changing with the advent of new treatment options that overcome some of the drawbacks of conventional AK field therapy. Typically, AK field therapy took weeks or months to complete, during which time patients often felt their appearance was cosmetically unacceptable. While

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